Relative Binding Affinities of Alkali Metal Cations to [18]Starand in Methanol: Computational and Experimental Studies

Abstract

The binding affinity and selectivity of a new ionophore, [1_8]starand (1), toward alkali metal cations in methanol were examined through NMR titration experiments and free energy perturbation (FEP) and molecular dynamics simulations. The preference was determined to be K^+ > Rb^+ > Cs^+ > Na^+ ≫ Li^+ in both FEP simulations and NMR experiments. The FEP simulation results were able to predict the relative binding free energies with errors less than 0.13 kcal/mol, except for the case between Li^+ and Na^+. The cation selectivity was rationalized by analyzing the radial distribution functions of the M−O and M−C distances of free metal cations in methanol and those of metal−ionophore complexes in methanol.